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Inhibition of LDHB triggers DNA damage and increases cisplatin sensitivity in pleural mesothelioma.

Pleural mesothelioma (PM) is an aggressive, asbestos-linked cancer with limited treatment options and a poor prognosis. Lactate dehydrogenase B (LDHB) converts lactate to pyruvate, and its silencing reduces mitochondrial metabolism, particularly nucleotide synthesis. However, whether and a role of LDHB in PM is unclear. This study aimed to investigate the effects of silencing LDHB in PM cells and their response to chemotherapy. LDHB was silenced using siRNA transfection and inducible shRNA constructs. Proliferation, colony formation, and cell viability were assessed, while DNA damage was analy…

mRNA-laden lipid nanoparticle-enabled humanized CD19 CAR-T-cell engineering for the eradication of leukaemic cells.

Chimeric antigen receptor T-cell (CAR-T) therapy has shown transformative potential in treating malignant tumours, with increasing global approval of CAR-T products. However, high-production costs and risks associated with viral vector-based CAR-T cells-such as insertional mutagenesis and secondary tumour formation-remain challenges. Our study introduces an innovative CAR-T engineering approach using mRNA delivered via lipid nanoparticles (LNPs), aiming to reduce costs and enhance safety while maintaining strong anti-tumour efficacy. We developed an LNP-based transfection protocol for efficien…

Construction of stable packaging cell lines for large-scale industrial BaEV-enveloped retroviral vector production.

INTRODUCTION: Viral vectors with Baboon endogenous virus (BaEV) envelope proteins have been demonstrated to markedly increase gene transfer efficiency to NK cells. Nevertheless, the cytotoxicity of the BaEV envelope protein necessitates the production of this type of viral vector by transient transfection, which significantly constrains its potential for large-scale industrial application. METHODS: In this study, we constructed a stably packed BaEV-PackRV cell line for BaEVenveloped retroviral vectors. This packaging cell line was constructed to stably express gag, pol, and BaEV envelope prot…

The MicroRNA miR-454 and the mediator complex component MED12 are regulators of the androgen receptor pathway in prostate cancer.

Prostate cancer that is resistant to anti-androgen treatment, such as enzalutamide, represents a therapeutic challenge. To study their molecular and functional features, the enzalutamide-resistant PCa cell lines LNCaP Abl EnzR and DuCaP EnzR constitute valuable in vitro models. In this work, we explored two different strategies for reducing AR/AR-V7/c-Myc. MED12 knockdown decreased the protein expression of AR, AR-V7 and c-Myc. Similarly, we identified AR and AR-V7 as targets of miR-454-3p. Concomitantly, the transfection of synthetic miR-454-3p reduced the protein expression of AR in both Enz…

Nanobody-Decorated Lipid Nanoparticles for Enhanced mRNA Delivery to Tumors In Vivo.

Prostate cancer (PCa) ranks as the fifth leading cause of cancer-related deaths among men worldwide. In 10-20% of the cases, PCa progresses … on the surface of 80% of LNPs. These anti-PSMA LNPs exhibit enhanced and specific uptake, and mRNA transfection in PSMA+ cancer cells both in vitro and in a Zebrafish (ZF) metastatic PCa xenograft model. Additionally, in a mouse PSMA-positive xenograft model, systemic administration results in increased LNP accumulation, but not functional mRNA delivery. Thes …

Pia Mater-Penetrable Lipopolymer Nanoparticles for Gliocyte-Targeted IL-10 mRNA Therapy Alleviate Paclitaxel-Induced Peripheral Neuropathy.

Paclitaxel (PTX) is a commonly used chemotherapeutic agent for treating various solid tumors; however, it often leads to a severe side effec … a mater. More importantly, this P6CIT LPNP demonstrates the ability to achieve highly targeted mRNA transfection in gliocytes within the spinal cord and dorsal root ganglia (DRG), which is essential for the regulation of neuroinflammation. Furthermore, two intrathecal injections of P6CIT LPNPs encapsulating mIL-10 (P6CIT/mIL-10) significantly alleviate PIPN by …

Carbon Dots with Tunable Charge as Mucus-Penetrating Gene Carriers.

Background/Objectives: Local delivery of gene therapy products through the airways shows great promise for the treatment of a number of seri … e functionalization of CDs with maleamic acid groups resulted in a 1000- to 10,000-fold increase in transfection efficiency in the mucus-producing model, offering new opportunities for lung gene therapy.

HMGB1 activates caspase-1 and induces hepatic stellate cell activation via GABPA-ASC.

In the intricate process leading to liver fibrosis, which frequently correlates with inflammation, the activation of hepatic stellate cells … ld prevent HMGB1-induced activation of HSCs. Through immunofluorescence, immunoblotting, lentiviral transfection, luciferase reporter assay and chromatin immunoprecipitation assay, it was found that HMGB1 activated caspase-1 through GABPA-regulated ASC transcription, which not only participates in the activation of caspase-1, but also promotes the process of l …

METTL3-mediated m6A modification regulates D-galactose-induced skin fibroblast senescence through miR-208a-5p.

INTRODUCTION: As the most abundant epitranscriptomic modification, N6-methyladenosine (m6A) critically influences aging and age-related pathologies. However, its regulatory interplay with microRNAs (miRNAs) in skin aging remains poorly defined. METHODS: Aging phenotypes were recapitulated using D-galactose (D-gal)-induced senescence models in mouse skin fibroblasts (MSFs) and mice. Interventions included METTL3 overexpression/knockdown, miR-208a-5p mimic/inhibitor transfection, and pharmacological mitophagy induction (GSK). Molecular analyses assessed m⁶A dynamics, gene regulation, and mitoch…

Анализ различных видов показывает, что гепатоциты кошки поддерживают ВИЧ-инфекцию.

Одной из серьезных проблем в области здравоохранения по-прежнему является вирус гепатита В (ГББВ), при этом число хронических инфекций составляет почти 300 млн. человек, однако исследованиям мешает отсутствие подходящих моделей для животных. Цель этого исследования состояла в том, чтобы выявить чувствительные к воздействию ВИЧ виды и создать новую модель инфекции. Первичные гепатоциты от людей, кошек, кроликов, сирийских хомяков, сибирских хомяков, морских свиней, быков, коз, свиней, циномольгуса макакаков и собак были оценены на наличие вируса гепатита D (HDV). Для оценки его восстановления н

Совпадение в аннотации оригинала
Hepatitis B virus (HBV) remains a major public health challenge, with nearly 300 million chronic infections, yet research is hindered by the … re assessed for HBV entry using hepatitis D virus (HDV) infection. HBV relaxed circular DNA (rcDNA) transfection was performed to evaluate its repair into covalently closed circular DNA (cccDNA). HBV infection assays were conducted in vitro. Results showed that primary hepatocytes from humans and cats were susceptible to HDV, suggesting their potential to supp …

MCP-1 Reduction by L-SIGN Expression in Dengue Virus-Infected Liver Endothelial Cells.

(1) Background: The C-type lectin domain family 4 member M (CLEC4M, also known as L-SIGN) is a crucial pathogen-recognition receptor for the … Results indicated that SK-HEP1 cells were more susceptible to DENV infection than MDDCs, and L-SIGN transfection significantly increased viral replication in SK-HEP1 cell lines. The study also found that L-SIGN-enhanced DENV infection is mediated by the decrease in monocyte chemoattractant protein-1 (MCP-1) but not interferon gamma inducible protein-10 (IP-10) …

IRS2/FOXO1 mitigates osteoarthritis by regulating chondrocyte autophagy and mitochondrial function.

PURPOSE: Osteoarthritis (OA) is a debilitating joint disease with no effective cure. This study investigates the role of Insulin Receptor Su … tology, qPCR, and Western blot. IRS2 was overexpressed in primary mouse chondrocytes via adenoviral transfection, with proliferation, apoptosis, and autophagy assessed by EdU, Annexin V/PI staining, and autophagy-related protein analysis. Adenovirus expressing Irs2 was injected intra-articularly into DMM mice, and cartilage integrity was assessed using histolo …

Novel Less Toxic, Lymphoid Tissue-Targeted Lipid Nanoparticles Containing a Vitamin B5-Derived Ionizable Lipid for mRNA Vaccine Delivery.

Following their approval by the Food and Drug Administration, lipid nanoparticles (LNPs) have emerged as promising tools for delivering mRNA … ipid I97. mRNA⊂LNP 5097 demonstrates favorable structural and physicochemical properties, high mRNA transfection efficiency, and long-term stability. Moreover, mRNA⊂LNP 5097 specifically delivers the mRNA to the spleen and lymph nodes in model mice, induces balanced Th1/Th2 immune responses, and elicits the production of high levels of neutralizing antibodies …

Successful treatment with selpercatinib after pralsetinib-related pneumonitis and intracranial failure in a patient with RET-rearranged nonsmall cell lung cancer.

Pralsetinib and selpercatinib are two highly potent and selective rearranged during transfection (RET) inhibitors that substantially improved the clinical outcome of patients with RET-rearranged non-small cell lung cancer. Treatment with one RET inhibitor after failure of the other is generally not recommended because of cross-resistance mechanisms. We report the case of a patient affected by metastatic RET-rearranged non-small cell lung cancer who experienced long-lasting disease control with pralsetinib. After 13 months from treatment start, the patient developed recurrent drug-related pneum…

Blood-to-Testis Transport of Ribavirin Involves Carrier-Mediated Processes at the Blood-Testis Barrier.

Ribavirin, an antiretroviral agent targeting the hepatitis C virus, causes male reproductive toxicity. This study investigated the mechanism … ptake was also observed in mouse ENT2-expressing Xenopus laevis oocytes, and gene silencing via the transfection of ENT2 small interfering RNA significantly reduced the [3H]ribavirin transport into TM4 cells by 13%. Taken together, these results suggest that ENT2 partially contributes to ribavirin transport at the BTB.

Tas2R143 regulates the expression of the Blood-Testis Barrier tight junction protein in TM4 cells through the NF-κB signaling pathway.

Although bitter receptors, known as Tas2Rs, have been identified in the testes and mature sperm, their expression in testicular Sertoli cell … ant downregulation (P < 0.05) in the expression of occludin and ZO-1 compared to both the siRNA-133 transfection group and the NF-κB inhibitors treatment group. These findings suggest that Tas2R143 likely regulates the expression of occludin and ZO-1 through the NF-κB signaling pathway and provides a theoretical basis for studying the regulatory mechanism of b …

Transcription factor DDIT3 is a potential driver in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal and aggressive tumor that affects the digestive tract, leading to high mortality … in PDAC cells, while being expressed at lower levels in normal pancreatic ductal epithelial cells. Transfection of short hairpin RNA targeting the DDIT3 gene reduced the proliferation, migration and invasion of PANC-1 cells. In vivo, in an in situ implantation tumor model with Pan02 cells, the size and weight of the tumors were reduced in the DDIT3 knockdown …

Intravenous and oral administration of the synthetic RNA drug, TY1, reverses heart failure with preserved ejection fraction in mice.

TY1, a synthetic non-coding RNA (ncRNA) bioinspired by small Y RNAs abundant in extracellular vesicles (EVs), decreases cGAS/STING activation in myocardial infarction and thereby attenuates inflammation. Motivated by the concept that heart failure with preserved ejection fraction (HFpEF) is a systemic inflammatory disease, we tested TY1 in a murine model of HFpEF. Intravenous TY1, packaged in a transfection reagent, reversed the cardiac and systemic manifestations of HFpEF in two-hit obese-hypertensive mice, without inducing weight loss. The effects of TY1 were specific, insofar as they were n…

GPR124 regulates murine brain embryonic angiogenesis and BBB formation by an intracellular domain-independent mechanism.

The GPR124/RECK/WNT7 pathway is an essential regulator of CNS angiogenesis and blood-brain barrier (BBB) function. GPR124, a brain endotheli … CD deletion impairs zebrafish angiogenesis, but paradoxically retains WNT7 signaling upon mammalian transfection. We thus investigated GPR124 ICD function using the mouse deletion mutant Gpr124ΔC. Despite inefficiently expressed GPR124ΔC protein, Gpr124ΔC/ΔC mice could be born with normal cerebral cortex angiogenesis, in comparison with Gpr124-/- embryonic let …

Allele-specific silencing of a dominant SETX mutation in familial amyotrophic lateral sclerosis type 4.

Amyotrophic lateral sclerosis 4 (ALS4) is an autosomal dominant motor neuron disease that is molecularly characterized by reduced R-loop lev … ely target the RNA transcript from the ALS4 allele containing the c.1166T>C mutation (p.Leu389Ser). Transfection of HEK293 cells with siRNA and plasmids encoding either wild-type or mutant (Leu389Ser) epitope tagged SETX revealed that three siRNAs specifically reduced mutant SETX protein levels without affecting the wild-type SETX protein. In ALS4 primary fibr …